BIOCHEMISTRY - L. Stryer - 1984

VOLUME 1

SECTION I. CONFORMATION AND DYNAMICS

CHAPTER 3. OXYGEN CARRIERS: MYOGLOBIN AND HEMOGLOBIN

3.15. Crucial Amino Acid Residues in Sequence

To date, Amino acid sequences of Hemoglobins from more than 20 animal species (ranging from lamprey to man) have been deciphered. The data reveal considerable amino acid diversity at most positions. However, there are 9 positions in the sequence occupied by the same Amino Acids in all or nearly all examined species (Table 3.2). These conserved (invariant) positions are of paramount importance for Hemoglobin function. Some of them are directly involved in the oxygen-binding site. Another conserved position is Tyrosine-HC2, which stabilizes the molecule by forming a Hydrogen bond between the H and F helices. Glycine (B6) is conserved owing to its small size: a side chain larger than a single hydrogen atom would prevent the close approach of the B and E helices (Fig. 3.27); Proline-C2 is essential as it serves to terminate the C helix.

Class="center">Table 3.2. Conserved amino acid residues in hemoglobin

The nonpolar residues in the interior of the hemoglobin molecule exhibit considerable Variability. In all cases, however, this involves the replacement of one nonpolar residue by another nonpolar one (e.g., Alanine by isoleucine). Thus, the distinctly nonpolar character of the interior of the molecule is preserved. As noted above, the Location OF THE heme in a nonpolar pocket, where it is shielded from Water, plays a crucial role in its reversible oxygenation. Furthermore, the presence of an internal nonpolar core in the hemoglobin molecule stabilizes its three-dimensional Structure.

Fig. 3.27. Crossing of the B and E chains in Myoglobin. Position B6 is occupied almost universally by glycine because there is no room for a side chain larger than that of glycine

Amino acid residues On the surface of the molecule are highly variable. In fact, very few of them maintain a constant positive or negative charge. One might expect proline residues to show constancy, as they serve to terminate helical regions. However, this is not the case. Only a single proline residue is invariant, yet in all myoglobins the respective lengths and orientations of the helices are virtually identical. Apparently, other mechanisms exist for the termination and bending of α-helices.

3.16. The Emergence of Hemoglobin—A New Evolutionary Milestone

So far, we have focused on the structural similarities between Myoglobin and hemoglobin. Functionally, however, these Two molecules are entirely distinct. The subunits of hemoglobin share the same overall fold as myoglobin. Yet the assembly of these subunits into an α₂β₂ tetramer gives rise to novel properties of immense biological significance. The next chapter is devoted to this subject.